1. Field of the Invention
The present invention relates to a novel human tumor-associated antigen, designated as placenta derived apoptotic factor (PDAF), and the genes thereof.
2. Description of the Prior Art
A number of cancer-specific genetic markers and tumor-associated antigens have been identified. It is found that tumor-associated antigens are mostly surface molecules that are expressed in tumor cells, instead of the cells of non-tumor tissues. Tumor-associated antigens have been characterized either as membrane proteins or altered carbohydrate molecules of glycoproteins and glycolipids. They make tumor cells immunologically distinct from normal cells, which are useful as diagnostic and therapeutic targets for human cancers.
Some tumor-associated antigens have been disclosed in prior references. For instance, a receptor-binding cancer antigen expressed on SiSo cells (RCAS1) functioning as a tumor-associated antigen, has been described by Takeshi Watanabe et al., 1999, Nature Medicine, Vol. 5, No. 8, pp.938-942. RCAS1 gene does not express in normal cells, but expresses in uterine cervical adenocarcinoma, uterine endomertrial adenocarcinoma, ovarian carcinoma and uterine cervical squamous cell carcinoma (see, Takeshi Watanabe et al., 1996, American Cancer Society, pp.1501-1509; and Hitoo Nakano, 1998, Clinical Cancer Research, vol. 4, pp. 1517-1520). In addition, the RCAS1 gene can also be expressed in esophageal squamous cell carcinoma, gastric adenocarcinoma, colon adenocarcinoma and pancreatic adenocarcinoma. RCAS1 is a protein comprising 213 amino acids. Such protein has an N-terminal transmembrane segments (8-27 amino acids) and a coiled-coil structure in the C-terminal portion (179-206 amino acids), indicating that RCAS1 may be a type II membrane protein or a secreted protein having a structure of dimeric protein. RCAS1 acts as a ligand for a putative receptor present on various human cell lines such as K562 (human chronic myelogeneous leukemia), CCRF-CEM (human T lymphoblast) and Ramos (Burkitt lymphoma) and normal peripheral lymphcytes such as T, B and NK cells. RCAS1 inhibits the growth of receptor-expressing cells and induces apoptotic cell death. Tumor cells may evade immune surveillance by expressing RCAS1 and induce apoptosis in RCAS1 receptor-positive immune cells. RCAS1 plays roles in both tumor-associated antigen and induction of apoptosis of the immune cells.
It is expected that new tumor-associated antigens, similar to the tumor-associated RCAS1 antigen and the nucleic acids coding for the antigens, are useful in diagnosing, preventing, and treating immune disorders, cell proliferation and tumors, particularly cancers.
One object of the invention is to provide a novel human tumor-associated antigen, designated as placenta derived apoptotic factor (PDAF), which comprises an amino acid sequence of SEQ ID NO:1 and the biologically functional equivalent.
One object of the invention is to provide a polypeptide comprising an amino acid sequence of SEQ ID NO:2 and the variants thereof.
One object of the invention is to provide a fragment of the PDAF, comprising an amino acid sequence of SEQ ID NO:3 and the biologically functional equivalent thereof.
Another object of the invention is to provide the nucleic acid of SEQ ID NO: 4 encoding the polypeptide of SEQ ID NO: 1 and the degenerate sequences thereof. Also, the invention provides the nucleic acid of SEQ ID NO: 5 encoding the polypeptide of SEQ ID NO: 2 and the degenerate sequences thereof; and the nucleic acid of SEQ ID NO: 6 encoding the polypeptide of SEQ ID NO: 3 and the degenerate sequences thereof.
Another object of the invention is to provide an expression vector containing the nucleic acid of SEQ ID NO: 4, and an expression vector containing the nucleic acid of SEQ ID NO: 6. In addition, the invention provides a host cell containing the nucleic acid of SEQ ID NO: 4 and a host cell containing the nucleic acid of SEQ ID NO: 6.
Another object of the invention is to provide a pharmaceutical composition comprising the PDAF of the invention, or the fragments thereof.
Another further object of the invention is to provide transgenic animals, which is introduced with a gene fragment containing the nucleic acid sequence of SEQ ID NO: 4, or a gene fragment containing the nucleic acid sequence of SEQ ID NO: 5, or a gene fragment containing the nucleic acid sequence of SEQ ID NO: 6.